Parade Publications Inc., a unit of the Newhouse family’s media empire, is pulling the plug on teen publication React.

Industry sources estimate the weekly magazine — aimed at teen boys and girls and inserted into Sunday newspapers — lost more than $50 million in its five-year run.

Walter Anderson, the chairman and publisher of Parade, blamed the lack of advertising support for the magazine’s demise.

“It was an editorial success — it was inserted into 225 papers with circulation of 4 million — but we were not able to reach the same success with the advertising community,” said Anderson.

Both the Web site and the magazine will be shut down after the June 5 issue, Anderson said. The post of editor of React has been vacant since last month, when Lee Kravitz was named to succeed Anderson as editor-in-chief of parent Parade.

Forty-two people will be given severance packages.

Anderson called the staff together yesterday to deliver the bad news.

“I wrestled with this for months, but it just did not work for us financially,” he said.

Teens have always been a tough market to reach, with boys considered particularly elusive. While Time Inc.’s Teen People has hit a responsive chord with teen girls, the other publications flooding the category segment have had mixed results. And five years ago, even Time Inc. stumbled when it tried to launch Mouth2Mouth as a dual-gender teen title.

“There’s never been a successful dual audience publication to the youth market,” said Martin Walker, an industry consultant. “A 16-year-old boy is a boy. A 16-year-old girl is a woman.”

There’s also a lack of advertising for the market. Most teen-magazine ads are fashion-oriented, while companies like McDonald’s prefer TV.Keith J. Kelly